Journal of pharmaceutical sciences
-
Randomized Controlled Trial Clinical Trial
Effect of dexmedetomidine on propofol requirements in healthy subjects.
Dexmedetomidine-propofol pharmacodynamic interaction was evaluated in nine healthy subjects in a crossover design. Dexmedetomidine/placebo was infused using a computer-controlled infusion pump (CCIP) to maintain a pseudo-steady-state plasma concentration of 0.66 +/- 0.080 or 0 ng/mL, respectively. Forty-five minutes after the dexmedetomidine/placebo infusion was started, propofol was infused using a second CCIP to achieve a stepwise logarithmically ascending propofol concentration (1.00 to 13.8 microg/mL) profile. ⋯ The apparent EC50 values of propofol (EC50APP; concentration of propofol at which the probability of achieving a pharmacodynamic endpoint is 50% in the presence of dexmedetomidine concentrations observed in the current study; dexmedetomidine treatment) were 0.273, 0.544-0.643, and 3.89 microg/mL for the ability to hold a syringe, sedation scores, and motor response, respectively. Dexmedetomidine reduced propofol concentrations required for sedation and suppression of motor response. Therefore, the propofol dose required for sedation and induction of anesthesia may have to be reduced in the presence of dexmedetomidine.